Tackling maladaptive memories through reconsolidation: From neural to clinical science - a summary of an article by Elsey& Kindt (2017).

Tackling maladaptive memories through reconsolidation: From neural to clinical science
By: Elsey, J. W. B. & Kindt, M. (2017).
Neurobiology of Learning and Memory, 142, 108-117

Memory reactivation can induce a labile period, during which previously consolidated memories are sensitive to change, and in need of restabilization. This is reconsolidation.
Memory labilization appears to result from the interplay of learning history, reactivation, and individual differences.

Memory reconsolidation

The dominant model of memory formation proposes that memories transition from a short-term and relatively unstable trace to a more persistent long-term form.
This transition from short-term memory to long-term memory is consolidation.
Consolidation is thought to be mediated by protein synthesis dependent synaptic changes.
Protein synthesis inhibitors (PSIs) prevent the expression of long-term memory when administered shortly after learning.
Once consolidated, memories appear insensitive to protein synthesis inhibition, and can prove highly recalcitrant to attempts at modification.

Reactivation of a memory can render it vulnerable to amnestic interventions.
Protein synthesis inhibition shortly after reactivation can prevent the later expression of long-ter memory.
Under certain conditions, a consolidated memory can be brought into a labile state by reactivation, during which the memory trace can be modified or even disrupted.
This labile state requires restabilization in a manner similar to consolidation.
The reactivation-induced period of lability is temporary.

The amnesia for auditory fear conditioning could be induced by the systemic administration of propranolol, timed to coincide with memory reactivation.
The blockade of beta-adrenergic receptors by propranolol is believed to indirectly inhibit protein synthesis by halting noradrenaline-stimulated CREB phosphorylation in the amygdala.

The disruption of reconsolidation by pharmacological means has been proven effective in both non-human animals and humans under controlled laboratory settings.

Reactivation and reconsolidation are not synonymous

Reconsolidation is most reliably induced by memory reactivations that in some way add to or indicate the need to update the memory.

Memory expression appears to be unnecessary for inferring memory reconsolidation.
NMDA receptor activation is necessary for the labiliation of a fear memory trace upon reactivation.
AMPA receptors are crucial for the expression of that memory.
These two processes are dissociable.

It is the prediction error, not the absence of reinforcement, that is necessary for the destabilizaiton of conditioned fear memories.

For the translation of reconsolidation-based research into clinical practice, simply generating a fear response or reactivating a patient’s memory may not trigger reconsolidation of the target memory trace.
An optimal reactivation session should involve some kind of prediction error.
Prediction errors could include not only the violation of expectations, but also the learning of additional information if learning has not reached asymptote.

Prediction error, reconsolidation, and extinction

Prediction error during reactivation is not always sufficient for the induction of reconsolidation.
When prediction error occurs, the length of reactivation or extent of prediction error can determine whether reconsolidation or extinction is the result.

Depending on when reactivation is terminated, one may induce reconsolidation, extinction, or a limited period between these two in which amnestic agents have no effect.
Which of these processes is triggered appears to be determined at the offset of the reactivation episode.

The extent of prediction error determined the fate of memory.

Induction of reconsolidation is a balancing act.

• Without prediction error, memory is not labilized and made vulnerable to amnestic agents
• With extended reactivation and multiple prediction errors, destabilization does not take place and extinction may even occur instead.

This is complicated by the learning history and temperament of the individual whose memory is being targeted.